. The overall specific aims of Dr. Vince's laboratory continue to be the synthesis and ultimate conversion of carbocyclic nucleosides into useful chemotherapeutic agents. The long range objective is to use previously developed synthetic approaches to other carbocyclic nucleosides and to study metabolic activation and inactivation as a basis for adjustment of active leads into highly effective agents. Two major categories of analogs divided into several subcategories will be prepared. These include: I, Dideoxydidehydro Nucleosides; a) 6-substituted-2aminopurine nucleosides with anti-HIV activities, b) triphosphates of the above compounds for kinetic studies with HIV reverse transcriptase, c) 8-aza purine derivatives with antitumor activities, d) 5'-sulfamoyl derivatives of a) and (c) with antitumor activities, e) aminoimidazole, fluoroimidazole, and 2-azapurine derivatives, and f) 5'-phosphonates of selected nucleoside for potential antiviral/antitumor activities. II, Analogs of intermediates in the Biosynthesis of Purine Nucleosides; a) inhibitors of phosphoribosyl glycineamide synthetase, b) inhibitors of glycineamide ribonucleotide transformylase, and c) inhibitors of AICAR transformylase. The compounds in each series will be prepared by methods outlined and will be tested for antitumor and antiviral activities. Tissue cultures presently availale in investigator's laboratory will be used for initial cytotoxicity studies against tumor cells. Compounds will be sent to the NCI for screening against a wide variety of human tumor cell lines. All compounds will be forwarded to NIH for anti-HIV screening. Compounds will also be screened for activity against DNA and RNA viruses, including herpes and influenza viruses. The compounds of group II will be tested for substrate and/or inhibitor activity on the purified de novo purine biosynthesis enzymes. The triphosphate derivatives will be used to explore the binding requirements of HIV reverse transcriptase using purified enzymes.